The protein TMEM173/STING (stimulator of interferon genes) (Ishikawa and Barber, 2008; Zhong et al. 2008; Sun et al. 2009; Burdette et al. 2011) is a central player in the innate immune response to nucleic acids, particularly cytosolic dsDNA (reviewed in Burdette and Vance, 2013). STING responds to various pathogens, as well as to mitochondrial damage, and its overactivation may contribute or possibly even trigger the onset of autoimmune disorders such as systemic lupus erythematosus. Drug discovery requires a mechanistic understanding of the cytosolic DNA-sensing pathway. Such discovery is desperately needed for development of agonists and antagonists of innate immunity, and will have a profound impact on anti-cancer and vaccine development, as well as therapies for autoimmune disorders.